Author information
1 Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire d'Angers, Angers, France; Laboratoire HIFIH, UPRES 3859, SFR 4208, Université d'Angers, Angers, France. Electronic address: JeBoursier@chu-angers.fr.
2 Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire de Toulouse, Toulouse, France; Institut CARDIOMET, Fédération Hospitalo-Universitaire IMPACT, Toulouse, France.
3 Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire Grenoble-Alpes, Grenoble, France; INSERM U1209, Université Grenoble-Alpes, Grenoble, France.
4 Service d'Hépatologie, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France.
5 Laboratoire HIFIH, UPRES 3859, SFR 4208, Université d'Angers, Angers, France.
6 Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire d'Angers, Angers, France; Laboratoire HIFIH, UPRES 3859, SFR 4208, Université d'Angers, Angers, France.
7 Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
8 Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire Grenoble-Alpes, Grenoble, France.
9 Laboratoire HIFIH, UPRES 3859, SFR 4208, Université d'Angers, Angers, France; Département de Pathologie Tissulaire et Cellulaire, Centre Hospitalier Universitaire d'Angers, Angers, France.
10 Service d'Anatomopathologie, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Pessac, France.
11 MINT UMR INSERM 1066, CNRS 6021, Angers Univeristy.
12 Service d'Hépatologie, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France; INSERM U1053, Université de Bordeaux, Bordeaux, France.
Abstract
BACKGROUND & AIMS:
Advanced liver fibrosis is an important diagnostic target in non-alcoholic fatty liver disease (NAFLD) as it defines the subgroup of patients with impaired prognosis. The non-invasive diagnosis of advanced fibrosis is currently limited by the suboptimal positive predictive value and the grey zone (representing indeterminate diagnosis) of fibrosis tests. The combination of fibrosis tests significantly improves the diagnosis of liver fibrosis in chronic hepatitis C. Here, we aimed to determine the best combination of non-invasive tests for the diagnosis of advanced fibrosis in NAFLD.
METHODS:
A total of 938 patients with biopsy-proven NAFLD were randomized 2:1 into derivation and validation sets. All patients had liver stiffness measurement with vibration controlled transient elastography (VCTE), blood fibrosis tests (NAFLD fibrosis score, FIB-4, Fibrotest, Hepascore, FibroMeter), and calculation of FibroMeterVCTE, which combines VCTE results and FibroMeter markers in a single test.
RESULTS:
For the diagnosis of advanced fibrosis, VCTE was significantly more accurate than the blood tests (area under the receiver operating characteristic curve [AUROC]: 0.840±0.013, p≤0.005) and among these latter, FibroMeter was the most accurate (AUROC: 0.793±0.015, p≤0.017). The combinatory test FibroMeterVCTE outperformed VCTE and blood tests (AUROC: 0.866±0.012, p ≤0.005). The sequential combination of FIB-4 then FibroMeterVCTE (FIB-4-FMVCTE algorithm) or VCTE then FibroMeterVCTE(VCTE-FMVCTE algorithm) provided an excellent 90% diagnostic accuracy for advanced fibrosis with a very low 20% rate of required liver biopsy. The FIB-4-FMVCTE and VCTE-FMVCTE algorithms were significantly more accurate than the pragmatic algorithms currently proposed.
CONCLUSION:
The sequential combination of fibrosis tests in the FIB-4-FMVCTE and VCTE-FMVCTE algorithms provides a highly accurate solution for the diagnosis of advanced fibrosis in NAFLD. These algorithms should be now validated for case finding of advanced liver fibrosis in diabetology or primary care settings.
LAY SUMMARY:
Liver fibrosis evaluation is mandatory in NAFLD as advanced fibrosis identifies the subgroup of patients with impaired prognosis. FibroMeterVCTE is a new fibrosis test combining blood markers (aspartate aminotransferase, gamma-GT, prothrombin time, platelets, alpha2-macroglobulin) and VCTE result in a single diagnostic test. Our results show that FibroMeterVCTEoutperforms the others blood fibrosis tests and VCTE for the diagnosis of advanced fibrosis in a large multi-centric cohort of 938 biopsy-proven NAFLD patients. Sequential algorithms using a simple blood test (FIB-4) or VCTE as a first-line procedure, then FibroMeterVCTE as a second-line test well classified 90% of patients for advanced fibrosis, with only 20% liver biopsy requirement.